This project is directed to the definition of function(s) and mechanism(s) of interaction(s) of macrophages (M phi), thymus-derived cells (T cells), and precursors of antibody-producing cells (B cells) in the generation and regulation of antibody responses in tissue culture. The antigen-presentation function of M phi will be analyzed with attention to the phi-membrane components involved, factors which control helper vs. suppressor T cell development, and mechanisms of genetic restrictions governing efficient M phi-immune T cell interactions in secondary responses. Several T cell-dependent antigens will be studied to determine whether these restrictions govern M phi-T cell interactions in responses to all T cell-dependent antigens or whether they are limited to antigens under H-2 linked, Ir gene control. Antisera against defined membrane components, such as H-2 and Ia antigens and Ig, which suppress antibody responses will be used to analyze the mechanisms of interactions among these cells and the critical factors involved in the switch from IgM to IgG antibody production. These investigations will further the understanding of fundamental mechanisms that regulate antibody responses. This understanding should lead to a better appreciation of mechanisms of disease processes with immunological components such as autoimmunity, and may lead to manipulations of the immune system to permit better protection against infectious agents and alleviate allergic diseases. BIBLIOGRAPHIC REFERENCES: Kapp, J.A., Pierce, C.W., and Benacerraf, B., Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). II. Cellular source and effect on responder and nonresponder mice. J. Exp. Med. 145:828-838, 1977. Pierce, C.W., Kapp, J.A., and Benacerraf, B., Genetic restrictions of macrophage-lymphocyte interactions in secondary antibody responses in vitro. Cold Springs Harbor Symposia on Quantitative Biology, XLI: 563-570, 1977.